Properties of melanin pigments for the definition of mechanisms of (photo)toxicity in red hair phenotype and development of strategies of (photo)protection.

In recent years particular attention has been focused on the properties of melanin pigments with regard to their association with some pathological conditions and to their controversial role in the response of skin to solar radiation. This is especially true in the case of pheomelanins, typical of red hair phenotype, with red hair pale skin, blue-green eyes and freckles. People exhibiting this phenotype have poor tanning capacity, exhibit a UV-susceptibility trait with high tendency to sunburn and an increased risk for skin tumors and melanoma. On the other hand, eumelanins are commonly believed to be the most important photoprotective factor, even if evidence accumulating over the last decades highlight a much more controversial role of eumelanins in human pigmentation. On these bases, the research work carried out during the PhD course and reported in this thesis was directed at investigating the light-independent effects of purified human hair melanins on keratinocyte cell cultures with particular attention to their pro-oxidant properties and at defining the origin of the broadband absorption spectrum of eumelanin, which underpins their protective shielding effect. Based on the consideration that, besides eumelanin pigments, the entire melanogenic pathway is relevant to melanocyte function, the effect of carboxyl group substituent of indole precursors on eumelanin properties was evaluated and a suitable derivative of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) was prepared to assess the photoprotective properties for potential application in sunscreen formulations. Local excess of pigmentation is one of the most common pigmentary disorder5 whose aesthetically impact has urged the search for efficient strategies for control of skin pigmentation. As a preliminary approach toward the implementation of a novel skin depigmenting agent a conjugate of caffeic acid with dihydrolipoic acid was prepared and tested for its ability to inhibit mushroom tyrosinase activity

Eumelanin broadband absorption develops from aggregation-modulated chromophore interactions under structural and redox control

Eumelanins, the chief photoprotective pigments in man and mammals, owe their black color to an unusual broadband absorption spectrum whose origin is still a conundrum. Excitonic effects from the interplay of geometric order and disorder in 5,6-dihydroxyindole (DHI)-based oligomeric/polymeric structures play a central role, however the contributions of structural (scaffold-controlled) and redox ( €-electron-controlled) disorder have remained uncharted. Herein, we report an integrated experimental-theoretical entry to eumelanin chromophore dynamics based on poly(vinyl alcohol)-controlled polymerization of a large set of 5,6-dihydroxyindoles and related dimers. The results a) uncover the impact of the structural scaffold on eumelanin optical properties, disproving the widespread assumption of a universal monotonic chromophore; b) delineate eumelanin chromophore buildup as a three-step dynamic process involving the rapid generation of oxidized oligomers, termed melanochromes (phase I), followed by a slow oxidant-independent band broadening (phase II) leading eventually to scattering (phase III); c) point to a slow reorganization-stabilization of melanochromes via intermolecular redox interactions as the main determinant of visible broadband absorption

“Fifty Shades” of Black and Red or How Carboxyl Groups Fine Tune Eumelanin and Pheomelanin Properties

Recent advances in the chemistry of melanins have begun to disclose a number of important structure-property-function relationships of crucial relevance to the biological role of human pigments, including skin (photo) protection and UV-susceptibility. Even slight variations in the monomer composition of black eumelanins and red pheomelanins have been shown to determine significant differences in light absorption, antioxidant, paramagnetic and redox behavior, particle morphology, surface properties, metal chelation and resistance to photo-oxidative wear-and-tear. These variations are primarily governed by the extent of decarboxylation at critical branching points of the eumelanin and pheomelanin pathways, namely the rearrangement of dopachrome to 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA), and the rearrangement of 5-S-cysteinyldopa o-quinoneimine to 1,4-benzothiazine (BTZ) and its 3-carboxylic acid (BTZCA). In eumelanins, the DHICA-to-DHI ratio markedly affects the overall antioxidant and paramagnetic properties of the resulting pigments. In particular, a higher content in DHICA decreases visible light absorption and paramagnetic response relative to DHI-based melanins, but markedly enhances antioxidant properties. In pheomelanins, likewise, BTZCA-related units, prevalently formed in the presence of zinc ions, appear to confer pronounced visible and ultraviolet A (UVA) absorption features, accounting for light-dependent reactive oxygen species (ROS) production, whereas non-carboxylated benzothiazine intermediates seem to be more effective in inducing ROS production by redox cycling mechanisms in the dark. The possible biological and functional significance of carboxyl retention in the eumelanin and pheomelanin pathways is discussed

Melanin pigmentation control by 1,3-thiazolidines: does NO scavenging play a critical role?

Thiazolidine MHY 384 and structurally related compounds previously described may operate through multiple mechanisms that overall contribute to their remarkable potency in the control of melanin pigmentation. It is difficult at present to assess which is the most critical target of the action of these compounds i.e. the MSH- CREB-MITF signaling pathway activating tyrosinase expression, tyrosinase activity itself , the early stages of the melanogenesis pathway or also the NO induced melanogenesis via control of CREB phosphorylation or by direct scavenging, but it is possible that such a variety of mechanisms of action may represent an advantage of this class of compounds over other proposed skin depigmenting agents providing a useful strategy allowing to improve clinical efficacy, reducing the duration of therapy and the risk of adverse effects

From Fish Waste to Value: An Overview of the Sustainable Recovery of Omega-3 for Food Supplements

The disposal of food waste is a current and pressing issue, urging novel solutions to implement sustainable waste management practices. Fish leftovers and their processing byproducts represent a significant portion of the original fish, and their disposal has a high environmental and economic impact. The utilization of waste as raw materials for the production of different classes of biofuels and high-value chemicals, a concept known as “biorefinery”, is gaining interest in a vision of circular economy and zero waste policies. In this context, an interesting route of valorization is the extraction of omega-3 fatty acids (ω-3 FAs) for nutraceutical application. These fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have received attention over the last decades due to their beneficial effects on human health. Their sustainable production is a key process for matching the increased market demand while reducing the pressure on marine ecosystems and lowering the impact of waste production. The high resale value of the products makes this waste a powerful tool that simultaneously protects the environment and benefits the global economy. This review aims to provide a complete overview of the sustainable exploitation of fish waste to recover ω-3 FAs for food supplement applications, covering composition, storage, and processing of the raw material